Biologic activities of growth hormone secretagogues in humans

Growth hormone secretagogues (GHSs) are synthetic peptidyl and nonpeptidyl molecules with strong, dose-dependent, and reproducible growth hormone (GH) releasing activity even after oral administration. GHSs release GH via acti ons on specific receptors (GHS-R) at the pituitary and, mainly, at the hypo thalamic levels. GHSs likely act as functional somatostatin antagonists and meantime enhance the activity of CH-releasing hormone (GHRH)-secreting neu rons. The CH-releasing effect of GHSs is independent of gender but undergoe s marked age-related variations. Estrogens play a major role in enhancing t he GH response to GHSs at puberty, which GHRH hypoactivity, somatostatinerg ic hyperactivity and impaired activity of the the putative GHS-like ligand and receptors probably explain the reduced GH-releasing effect of GHSs in a ging. The activity of GHSs is not fully specific for CH. Their slight prola ctin-releasing activity probably comes from direct pituitary action. In phy siological conditions, the ACTH-releasing activity of GHSs is dependent on central actions; a direct action on GHS-R in pituitary ACTH-secreting tumor s likely explains the peculiar ACTH and cortisol hyperresponsiveness to GHS s in Gushing disease. GHSs have specific receptor subtypes in other central and peripheral endocrine and nonendocrine tissues mediating CH-independent biologic activities. GHSs influence sleep pattern, stimulate food intake, and have cardiovascular activities. GHs have specific binding in normal and neoplastic follicular derived human thyroid tissue and inhibit the prolife ration of follicular-derived neoplastic cell lines. The discovery of ghreli n, a 28 amino acid peptide synthesized in the stomach but also in other tis sues, has opened new fascinating perspectives of research in this field.